Identification of Tumor‐Specific Surface Proteins Enables Quantification of Extracellular Vesicle Subtypes for Early Detection of Pancreatic Ductal Adenocarcinoma
Abstract Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer‐related mortality, largely due to late‐stage diagnosis. Reliable early detection methods are critically needed. PDAC‐derived extracellular vesicles (EVs) carry molecules that reflect their parental tumor cells and are dete...
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2025-06-01
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| Online Access: | https://doi.org/10.1002/advs.202414982 |
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| author | Chen Zhao Zhili Wang Hyoyong Kim Hui Kong Junseok Lee Jacqueline Ziqian Yang Anmin Wang Ryan Y. Zhang Yong Ju Jina Kim Bing Feng Dejun Liu Yating Zhang Zhenfang Wang Yandong Zhang Shujing Guo Dekang Gao James S. Tomlinson Renjun Pei Jipeng Wan Stephen J. Pandol Myung‐Shin Sim Sungyong You Ding Ma Shaohua Lu Na Sun Hsian‐Rong Tseng Yazhen Zhu |
| author_facet | Chen Zhao Zhili Wang Hyoyong Kim Hui Kong Junseok Lee Jacqueline Ziqian Yang Anmin Wang Ryan Y. Zhang Yong Ju Jina Kim Bing Feng Dejun Liu Yating Zhang Zhenfang Wang Yandong Zhang Shujing Guo Dekang Gao James S. Tomlinson Renjun Pei Jipeng Wan Stephen J. Pandol Myung‐Shin Sim Sungyong You Ding Ma Shaohua Lu Na Sun Hsian‐Rong Tseng Yazhen Zhu |
| author_sort | Chen Zhao |
| collection | DOAJ |
| description | Abstract Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer‐related mortality, largely due to late‐stage diagnosis. Reliable early detection methods are critically needed. PDAC‐derived extracellular vesicles (EVs) carry molecules that reflect their parental tumor cells and are detectable in early disease stages, offering a promising noninvasive diagnostic approach. Here, a streamlined PDAC EV Surface Protein Assay for quantifying PDAC EV subpopulations in 300‐µL plasma through a two‐step workflow is presented: i) click chemistry‐mediated EV enrichment using EV Click Beads and trans‐cyclooctene‐grafted antibodies targeting three PDAC EV‐specific surface proteins (MUC1, EGFR, and TROP2), and ii) quantification of enriched PDAC EVs through reverse transcription‐quantitative polymerase chain reaction. The three PDAC EV‐specific surface proteins are identified using a bioinformatics framework and validated on PDAC cell lines and tissue microarrays. The resultant PDAC EV Score, derived from signals of the three PDAC EV subpopulations, demonstrates robust differentiation of PDAC patients from noncancer controls, with area under the receiver operating characteristic curves of 0.94 in the training (n = 124) and 0.93 in the validation (n = 136) cohorts. This EV‐based diagnostic approach successfully exploits PDAC EV subpopulations as novel biomarkers for PDAC early detection, translating PDAC surface proteins into an EV‐based liquid biopsy platform. |
| format | Article |
| id | doaj-art-c5a3209d5d17476085ddd9fac0939cdd |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Wiley |
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| series | Advanced Science |
| spelling | doaj-art-c5a3209d5d17476085ddd9fac0939cdd2025-08-20T03:24:39ZengWileyAdvanced Science2198-38442025-06-011221n/an/a10.1002/advs.202414982Identification of Tumor‐Specific Surface Proteins Enables Quantification of Extracellular Vesicle Subtypes for Early Detection of Pancreatic Ductal AdenocarcinomaChen Zhao0Zhili Wang1Hyoyong Kim2Hui Kong3Junseok Lee4Jacqueline Ziqian Yang5Anmin Wang6Ryan Y. Zhang7Yong Ju8Jina Kim9Bing Feng10Dejun Liu11Yating Zhang12Zhenfang Wang13Yandong Zhang14Shujing Guo15Dekang Gao16James S. Tomlinson17Renjun Pei18Jipeng Wan19Stephen J. Pandol20Myung‐Shin Sim21Sungyong You22Ding Ma23Shaohua Lu24Na Sun25Hsian‐Rong Tseng26Yazhen Zhu27Department of Pathology and Laboratory Medicine David Geffen School of Medicine, University of California, Los Angeles (UCLA) Los Angeles CA 90095 USACAS Key Laboratory for Nano‐Bio Interface Suzhou Institute of Nano‐Tech and Nano‐Bionics Chinese Academy of Sciences Suzhou 215123 ChinaCalifornia NanoSystems Institute Crump Institute for Molecular Imaging Department of Molecular and Medical Pharmacology David Geffen School of Medicine University of California, Los Angeles (UCLA) Los Angeles CA 90095 USADepartment of Pathology Zhongshan Hospital Fudan University Shanghai 200032 ChinaCalifornia NanoSystems Institute Crump Institute for Molecular Imaging Department of Molecular and Medical Pharmacology David Geffen School of Medicine University of California, Los Angeles (UCLA) Los Angeles CA 90095 USACalifornia NanoSystems Institute Crump Institute for Molecular Imaging Department of Molecular and Medical Pharmacology David Geffen School of Medicine University of California, Los Angeles (UCLA) Los Angeles CA 90095 USADepartment of Pathology and Laboratory Medicine David Geffen School of Medicine, University of California, Los Angeles (UCLA) Los Angeles CA 90095 USACalifornia NanoSystems Institute Crump Institute for Molecular Imaging Department of Molecular and Medical Pharmacology David Geffen School of Medicine University of California, Los Angeles (UCLA) Los Angeles CA 90095 USACalifornia NanoSystems Institute Crump Institute for Molecular Imaging Department of Molecular and Medical Pharmacology David Geffen School of Medicine University of California, Los Angeles (UCLA) Los Angeles CA 90095 USADepartment of Urology and Computational Biomedicine Cedars‐Sinai Medical Center Los Angeles CA 90048 USACalifornia NanoSystems Institute Crump Institute for Molecular Imaging Department of Molecular and Medical Pharmacology David Geffen School of Medicine University of California, Los Angeles (UCLA) Los Angeles CA 90095 USADepartment of Biliary‐Pancreatic Surgery Renji Hospital Shanghai Jiaotong University Shanghai 200217 ChinaDepartment of Anesthesiology Nanfang Hospital Southern Medical University Guangzhou 510515 ChinaDepartment of Pathology School of Basic Medical Sciences Southern Medical University Guangzhou 510515 ChinaDepartment of Pathology School of Basic Medical Sciences Southern Medical University Guangzhou 510515 ChinaDepartment of Pathology School of Basic Medical Sciences Southern Medical University Guangzhou 510515 ChinaDepartment of General Surgery Second Affiliated Hospital of Soochow University Suzhou 215004 ChinaDepartment of Surgery David Geffen School of Medicine, University of California, Los Angeles (UCLA) Los Angeles CA 90095 USACAS Key Laboratory for Nano‐Bio Interface Suzhou Institute of Nano‐Tech and Nano‐Bionics Chinese Academy of Sciences Suzhou 215123 ChinaCalifornia NanoSystems Institute Crump Institute for Molecular Imaging Department of Molecular and Medical Pharmacology David Geffen School of Medicine University of California, Los Angeles (UCLA) Los Angeles CA 90095 USADivision of Gastroenterology and Hepatology Department of Medicine Cedars‐Sinai Medical Center Los Angeles CA 90048 USADepartment of Urology and Computational Biomedicine Cedars‐Sinai Medical Center Los Angeles CA 90048 USADepartment of Urology and Computational Biomedicine Cedars‐Sinai Medical Center Los Angeles CA 90048 USADepartment of Biliary‐Pancreatic Surgery Renji Hospital Shanghai Jiaotong University Shanghai 200217 ChinaDepartment of Pathology Zhongshan Hospital Fudan University Shanghai 200032 ChinaCAS Key Laboratory for Nano‐Bio Interface Suzhou Institute of Nano‐Tech and Nano‐Bionics Chinese Academy of Sciences Suzhou 215123 ChinaCalifornia NanoSystems Institute Crump Institute for Molecular Imaging Department of Molecular and Medical Pharmacology David Geffen School of Medicine University of California, Los Angeles (UCLA) Los Angeles CA 90095 USADepartment of Pathology and Laboratory Medicine David Geffen School of Medicine, University of California, Los Angeles (UCLA) Los Angeles CA 90095 USAAbstract Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer‐related mortality, largely due to late‐stage diagnosis. Reliable early detection methods are critically needed. PDAC‐derived extracellular vesicles (EVs) carry molecules that reflect their parental tumor cells and are detectable in early disease stages, offering a promising noninvasive diagnostic approach. Here, a streamlined PDAC EV Surface Protein Assay for quantifying PDAC EV subpopulations in 300‐µL plasma through a two‐step workflow is presented: i) click chemistry‐mediated EV enrichment using EV Click Beads and trans‐cyclooctene‐grafted antibodies targeting three PDAC EV‐specific surface proteins (MUC1, EGFR, and TROP2), and ii) quantification of enriched PDAC EVs through reverse transcription‐quantitative polymerase chain reaction. The three PDAC EV‐specific surface proteins are identified using a bioinformatics framework and validated on PDAC cell lines and tissue microarrays. The resultant PDAC EV Score, derived from signals of the three PDAC EV subpopulations, demonstrates robust differentiation of PDAC patients from noncancer controls, with area under the receiver operating characteristic curves of 0.94 in the training (n = 124) and 0.93 in the validation (n = 136) cohorts. This EV‐based diagnostic approach successfully exploits PDAC EV subpopulations as novel biomarkers for PDAC early detection, translating PDAC surface proteins into an EV‐based liquid biopsy platform.https://doi.org/10.1002/advs.202414982cancer diagnosisextracellular vesiclesliquid biopsypancreatic ductal adenocarcinoma |
| spellingShingle | Chen Zhao Zhili Wang Hyoyong Kim Hui Kong Junseok Lee Jacqueline Ziqian Yang Anmin Wang Ryan Y. Zhang Yong Ju Jina Kim Bing Feng Dejun Liu Yating Zhang Zhenfang Wang Yandong Zhang Shujing Guo Dekang Gao James S. Tomlinson Renjun Pei Jipeng Wan Stephen J. Pandol Myung‐Shin Sim Sungyong You Ding Ma Shaohua Lu Na Sun Hsian‐Rong Tseng Yazhen Zhu Identification of Tumor‐Specific Surface Proteins Enables Quantification of Extracellular Vesicle Subtypes for Early Detection of Pancreatic Ductal Adenocarcinoma Advanced Science cancer diagnosis extracellular vesicles liquid biopsy pancreatic ductal adenocarcinoma |
| title | Identification of Tumor‐Specific Surface Proteins Enables Quantification of Extracellular Vesicle Subtypes for Early Detection of Pancreatic Ductal Adenocarcinoma |
| title_full | Identification of Tumor‐Specific Surface Proteins Enables Quantification of Extracellular Vesicle Subtypes for Early Detection of Pancreatic Ductal Adenocarcinoma |
| title_fullStr | Identification of Tumor‐Specific Surface Proteins Enables Quantification of Extracellular Vesicle Subtypes for Early Detection of Pancreatic Ductal Adenocarcinoma |
| title_full_unstemmed | Identification of Tumor‐Specific Surface Proteins Enables Quantification of Extracellular Vesicle Subtypes for Early Detection of Pancreatic Ductal Adenocarcinoma |
| title_short | Identification of Tumor‐Specific Surface Proteins Enables Quantification of Extracellular Vesicle Subtypes for Early Detection of Pancreatic Ductal Adenocarcinoma |
| title_sort | identification of tumor specific surface proteins enables quantification of extracellular vesicle subtypes for early detection of pancreatic ductal adenocarcinoma |
| topic | cancer diagnosis extracellular vesicles liquid biopsy pancreatic ductal adenocarcinoma |
| url | https://doi.org/10.1002/advs.202414982 |
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